Combined physiological and inflammatory biomarker assessment for risk stratification in moderate-to-severe asthma

<bold>Introduction:</bold> Oscillometry identifies small airways dysfunction as resistance between 5 and 20Hz (Rrs5-20) and area under reactance curve (AX). We hypothesised that integrating physiological indices such as Rrs5-20, AX and FEV1 with inflammatory biomarkers including FeNO and blood eosinophil count (BEC) might better stratify exacerbation risk in persistent asthma. <bold>Methods:</bold> 1012 moderate-to-severe asthma patients from the Oscillometry Asthma Registry (discovery cohort, n=617) and the ATLANTIS study (<ext-link>NCT02123667</ext-link>, validation cohort, n=395) were included. <bold>Results:</bold> In the discovery analyses, the adjusted odds ratio (aOR) [95%CI] for ≥1 exacerbation in the previous 12 months was 7.36 (3.63,14.93) p<0.001 for the triple FeNO≥25ppb, BEC≥300cells/µL and Rrs5-20≥0.10kPa/L/s phenotype, compared to 2.03 (1.26, 3.26) p<0.01 for the dual FeNO and BEC phenotype, with non-overlapping 95%CIs suggesting statistical significance (<bold>Figure</bold>). This was externally validated for exacerbations in the following 12 months in the prospective validation analyses (<bold>Figure</bold>). Analyses with AX (not shown) demonstrated similar results. <bold>Conclusion:</bold> The present results highlight the added value of fully characterizing asthma phenotypes using a combination of small airway physiology parameters and type 2 biomarkers. If further validated, this immune-physiological composite score could be used as a clinical risk-stratification tool. <fig><object-id>erj;66/suppl_69/PA3636/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

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Published
2025-09-27
DOI
https://doi.org/10.1183/13993003.congress-2025.pa3636
Primary Topic
Asthma and respiratory diseases
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article
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article

Combined physiological and inflammatory biomarker assessment for risk stratification in moderate-to-severe asthma

Stanley P. Galant, Maarten van den Berge, Salman Siddiqui, Leonardo M. Fabbri et al.
Asthma and respiratory diseases
article

Combined physiological and inflammatory biomarker assessment for risk stratification in moderate-to-severe asthma

Stanley P. Galant, Maarten van den Berge, Salman Siddiqui, Leonardo M. Fabbri, Stephen James Fowler, Janwillem Kocks, Rory Chan, Alvise Berti, Klaus F. Rabe, Alberto Papi, Pasquale Comberiati, Chris Ruiwen Kuo, Christopher Edward Brightling, Brian J. Lipworth, Apostolos Bossios, Ronald J. Dandurand, Omar S. Usmani, Francesco Menzella, Zuzana Diamant, Sundeep Salvi, Laura Ventura, Monica Kraft, Kathryn Prior, Dave Singh, Marcello Cottini
article en

Abstract

<bold>Introduction:</bold> Oscillometry identifies small airways dysfunction as resistance between 5 and 20Hz (Rrs5-20) and area under reactance curve (AX). We hypothesised that integrating physiological indices such as Rrs5-20, AX and FEV1 with inflammatory biomarkers including FeNO and blood eosinophil count (BEC) might better stratify exacerbation risk in persistent asthma. <bold>Methods:</bold> 1012 moderate-to-severe asthma patients from the Oscillometry Asthma Registry (discovery cohort, n=617) and the ATLANTIS study (<ext-link>NCT02123667</ext-link>, validation cohort, n=395) were included. <bold>Results:</bold> In the discovery analyses, the adjusted odds ratio (aOR) [95%CI] for ≥1 exacerbation in the previous 12 months was 7.36 (3.63,14.93) p<0.001 for the triple FeNO≥25ppb, BEC≥300cells/µL and Rrs5-20≥0.10kPa/L/s phenotype, compared to 2.03 (1.26, 3.26) p<0.01 for the dual FeNO and BEC phenotype, with non-overlapping 95%CIs suggesting statistical significance (<bold>Figure</bold>). This was externally validated for exacerbations in the following 12 months in the prospective validation analyses (<bold>Figure</bold>). Analyses with AX (not shown) demonstrated similar results. <bold>Conclusion:</bold> The present results highlight the added value of fully characterizing asthma phenotypes using a combination of small airway physiology parameters and type 2 biomarkers. If further validated, this immune-physiological composite score could be used as a clinical risk-stratification tool. <fig><object-id>erj;66/suppl_69/PA3636/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

University of Pisa (IT), University of Bergamo (IT), Lancashire Teaching Hospitals NHS Foundation Trust (GB), Children's Hospital of Orange County (US), Mount Sinai Health System (US), University Medical Center Groningen (NL), Karolinska University Hospital (SE), University of Padua (IT), University of Groningen (NL), University of Dundee (GB), University of Trento (IT), University of Ferrara (IT), BAIF Development Research Foundation (IN), McGill University Health Centre (CA), Ospedale Santa Chiara (IT), Manchester University NHS Foundation Trust (GB), NHS Grampian (GB), General Practitioners Research Institute (NL), AULSS 2 Marca Trevigiana (IT), Lung Institute (US), Dialyse Centrum Groningen (NL), Provincia Autonoma di Trento (IT), Center for Translational Neurophysiology of Speech and Communication (IT), LungenClinic Grosshansdorf (DE), Fondazione Poliambulanza Istituto Ospedaliero (IT), NIHR Manchester Biomedical Research Centre (GB), NIHR Leicester Biomedical Research Centre (GB)
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Asthma and respiratory diseases
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